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Severe Allergic Reactions Are Rare with COVID-19 mRNA Vaccines

Key findings

  • This study evaluated associations between previous allergic reactions and allergic reactions after mRNA COVID-19 vaccination; it involved 52,998 employees of Mass General Brigham, which comprises 16 health care institutions in the Boston area
  • Severe allergic reactions to an mRNA COVID-19 vaccine were rare (0.3%)
  • The 474 employees in the high-risk allergy group (those who reported a previous severe allergic reaction) were 2.5 times more likely than other employees to have an allergic reaction of any severity. The highest relative risks were for hives or swelling
  • The high-risk allergy group was a five-fold increased risk of severe reactions, but 94% received both doses of vaccine, and the occurrence of allergic reactions was consistently lower after the second dose
  • 97.6% of all employees received two doses of vaccine

Within days after COVID-19 vaccines began to be administered in December 2020, there were several reports of severe allergic reactions. That generated widespread concern and has contributed to vaccine hesitancy, particularly among people with a history of severe allergic reactions to another vaccine or medication.

Kimberly G. Blumenthal, MD, MSc, quality and safety officer for Allergy and co-director of the Clinical Epidemiology Program in the Division of Rheumatology, Allergy and Immunology at Massachusetts General Hospital, Lily Li, MD, associate physician in the Division of Allergy and Clinical Immunology at Brigham and Women's Hospital, and colleagues followed up on 52,998 employees at Mass General Brigham who received the mRNA COVID-19 vaccines (Pfizer–BioNTech or Moderna).

Their report in JAMA Network Open notes an increased risk of allergic reactions in employees who reported a previous severe allergic reaction. However, severe reactions to the COVID-19 vaccines were rare.

Study Methods

Employees were included in the study if they received at least one dose of an mRNA vaccine at Mass General Brigham and completed a post-vaccination symptom survey within three days. The study period was from December 14, 2020, to February 1, 2021, and follow-up was conducted through March 1, 2021.

Overall Results

2,516 employees (4.7%) reported one or more allergy symptoms, most commonly:

  • Mild symptoms, such as rash or itching (other than at the injection site)—2.7%
  • Wheezing, chest tightness or shortness of breath—1.3%
  • Hives—0.9%
  • Swollen lips, tongue, eyes or face—0.6%

High-Risk Allergy Group

On a pre-vaccination questionnaire, 474 employees reported a previous severe allergic reaction and were designated the "high-risk allergy group." They were:

  • 2.5 times more likely than other vaccinated employees to have any allergic reaction to vaccination
  • 3.8 times more likely to develop hives
  • 4.4 times more likely to develop swollen lips, tongue, eyes or face

The occurrence of these symptoms did not vary by sex, age, race or vaccine manufacturer.

Severe Allergic Reactions

Only 140 employees (0.3%) reported a severe allergic reaction to the COVID-19 vaccination. Six of them were from the high-risk allergy group.

65 of the 140 employees were seen by a Mass General Brigham allergist or immunologist, who confirmed an allergic reaction in 41 of them. The others actually had non-allergic symptoms such as dizziness, fever, chills, fast heart rate or headache.

The high-risk group was five times more likely than other employees to have a severe allergic reaction to COVID-19 vaccination. Still, 445 employees in the high-risk group (94%) had both doses of vaccine. The occurrence of allergic symptoms was consistently lower after the second dose.

Making the Decision

The U.S. government guidelines about mRNA COVID-19 vaccination list two reasons to consider not having the first or second dose:

  • Allergic reaction to a previous dose—Yet in this study, 51,706 employees (97.6%) received both vaccine doses, sometimes despite severe or nonsevere reactions to the first dose. (And it's possible that not all first-dose reactions were truly allergic)
  • Previous severe or immediate allergic reaction to any vaccine ingredient—The mRNA COVID-19 vaccines contain polyethylene glycol (PEG). The rare individuals who have previously reacted to a drug formulation containing PEG should consult an allergist or immunologist. In this study, nine employees reported a previous severe allergic reaction to PEG and were safely vaccinated, eight of them after being cleared by an allergist

Thus, the federal guidance is not absolute. Individuals who have concerns should consult their physician and share in the decision-making about whether to be vaccinated.

Learn more about COVID-19 research at Mass General

Refer a patient to the Division of Rheumatology, Allergy and Immunology

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New data on vaccinations among employees at Mass General Brigham has alleviated some concern about the safety of mRNA-based COVID-19 vaccines.


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